Is BCOR p.Arg763Trp (c.2287C>T) pathogenic?

BCOR p.Arg763Trp (c.2287C>T) is classified Uncertain significance in BCOR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-31). AlphaMissense: likely benign (0.2539); Very rare (popmax 0.00524%, afr); Associated with Inborn genetic diseases.

What condition is associated with BCOR p.Arg763Trp (c.2287C>T)?

BCOR p.Arg763Trp (c.2287C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BCOR p.Arg763Trp (c.2287C>T) in the general population?

BCOR p.Arg763Trp (c.2287C>T) is very rare (popmax 0.00524%, afr) (gnomAD).

What do computational predictors say about BCOR p.Arg763Trp (c.2287C>T)?

AlphaMissense predicts likely benign (score 0.2539) — an in-silico prediction, not a clinical call.

BCOR p.Arg763Trp

c.2287C>T · rs780348147 · VCV265045

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2539 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00524%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2539	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,116 bp · p 0.013 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00524% African / African-American · 3/57,256 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000685%

Overall 0.000991% 12/1,210,468 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00524%	19,085
South Asian	0.00176%	56,833
European (non-Finnish)	0.000894%	111,916

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BCOR
Protein: p.Arg763Trp
Coding: c.2287C>T
MANE Select: NM_001123385
dbSNP: rs780348147
Type: single nucleotide variant
Location: chrX:40073059 (GRCh38)
Structure: AlphaFold pLDDT 39.82 · 5 PDB

Full BCOR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCOR p.Arg763Leu Benign/Likely benign ★★ same residue
BCOR p.Arg763Gln Likely benign ★ same residue
BCOR p.Arg810Ter Pathogenic ★★ same condition
BCOR p.Ala1314Asp Uncertain significance ★★ ⚠ same condition
BCOR p.Ala147Thr Uncertain significance ★★ ⚠ same condition
BCOR p.Ala165Pro Uncertain significance ★★ ⚠ same condition
BCOR p.Arg1231Trp Uncertain significance ★★ ⚠ same condition
BCOR p.Asn193Ser Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/bcor-p-arg763trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown